Intensive versus Guideline Blood Pressure and Lipid Lowering in Patients with Previous Stroke: Main Results from the Pilot 'Prevention of Decline in Cognition after Stroke Trial' (PODCAST) Randomised Controlled Trial.

Philip M Bath,Joanna M Wardlaw,Clive Ballard,Nikola Sprigg,Sandeep Ankolekar,Jonathan Mant,Podcast Trial Investigators ,Gary A Ford,Daniel J Blackburn,John Reckless,Kailash Krishnan,Peter Passmore,Rob Stewart,Stuart Pocock,Polly Scutt,Alistair Burns

doi:10.1371/journal.pone.0164608

Abstract

BackgroundStroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial.MethodsIn a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125–170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0–8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke’s Cognitive Examination-Revised (ACE-R).ResultsWe enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1–48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference –10·6/–5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference –0·54/–0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison.ConclusionIn patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted.Trial RegistrationISRCTN ISRCTN85562386

Highlights

Stroke is complicated by cognitive impairment in up to 92% of survivors,[1] and dementia in 30%
Mean blood pressure (BP) was significantly reduced with intensive compared to guideline treatment, as was total/LDL-cholesterol with intensive lipid lowering compared to guideline
The Addenbrooke’s Cognitive Examination-R (ACE-R) score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6, and lipid lowering 4.4

Summary

Introduction

Stroke is complicated by cognitive impairment in up to 92% of survivors,[1] and dementia in 30%. Post stroke cognitive impairment (PSCI) more commonly affects executive dysfunction, and is associated with increased mortality and decreased quality of life.[2, 3] Despite these serious complications, which are devastating to patients and their family and economically costly to society, the evidence base for the prevention of PSCI and post-stroke dementia (PSD) is limited. Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial

Methods

Results

Conclusion